Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Hello Dr. Sher, just a little background- I am 39, Amh 1.23, fsh around 7, full term baby from a PGD/PGS embryo 2.5 years ago; I have done a total of 12 retrevials, 5 transfers; I have lost 7 of 8 PGD/PGS normal embryos; husband has Huntingtons Disease hence the PGD; no endo and tested for all immune issues- I just stopped doing PGS to give my embies a chance my last round. I am planing on transferring an untested 3BC, a monosomy 16, and a monosomy 22. The monosomys are from previous cycles. I just would like confirmation that a monosomy will not implant if it is a true monosomy. I do not want to take a chance on a late miscarriage if possible with a monosomy. Please let me know your thoughts on transferring these monosomys. I know it’s not ideal but I am at the end of my road. Thank you in advance.
There is no assurance but yes, the vast majority of autosomal monosomy embryos will not implant and those that do will almost always miscarry…usually early in pregnancy. The bigger question in your case is why so many failures with euploid embryos???
Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1.Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2.Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3.The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4.Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a.A“ thin uterine lining”
b.A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c.Immunologic implantation dysfunction (IID)
d.Endocrine/molecular endometrial receptivity issues
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
•The Fundamental Requirements for Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Blastocyst Embryo Transfers should be the Standard of Care in IVF
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•IVF Failure and Implantation Dysfunction:
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF?
•The Role of Nutritional Supplements in Preparing for IVF
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Ge
Hello Dr I just had my betas drawn at 13 dpo and they were only 24! I’m super nervous because about 9 months ago I had a chemical at 5 weeks so I could really use the input. Thanks!
I wish I could be encouraging. It is possible this will work out but the odds are not great with such a low number. Repeat in 2 days.
Geoff Sher
Dr Sher what is your opinion on ET without use of ultrasound guidance? I have recently had a fresh ET without use of ultrasound guidance & I am feeling quite hopeless about it. What is the likelihood of success doing ET without Ultrasound?
Respectfully,
In my opinion an US guided ET is the standard of care!
Geoff Sher
How much for tubal reversal
Dont know. We do not do Tubal Reversal. IVF is by far preferable.
There is a relatively high success rates following tubal re-connection (reanastomosisis) in cases of previous tubal ligation (a birth rate of +/- 50% within 3 years of a successful surgery). However, IVF performed in a center of excellence produces almost the same success rate following a single attempt and is far less invasive than surgery. IVF also does not require general anesthesia, hospitalization, or a protracted time off work. Moreover by doing IVF and leaving the tubal ligation undisturbed, the woman retains subsequent control over family planning without having to resort to using some other form of contraception. Another point to be considered is the high incidence of tubal or ectopic pregnancy following the performance of tubal reanastomosisis high (about 20%).Major surgery also requires a few days of hospitalization and subsequently a few weeks of convalescence. There is also a risk of post-operative complications, increased cost, and time away from work, incapacitation, and significantly greater discomfort. The cost of a full cycle of IVF is in fact comparable to that of tubal reanastamosisis.
In my opinion, provided that IVF is performed in a program with high success rates, tubal surgery for fixing damaged or blocked Fallopian tubes, with few exceptions, can no longer be justified financially or ethically.
Geoff Sher
800-780-7437
Dear Dr. Sher,
I appreciate your blog very much and have learned a lot from your insights. My husband and I have been ttc for 16 cycles with no luck. I am 37, but my doctor hasn’t been able to pinpoint a cause for infertility. Luckily, I had 2 egg retrievals when I was 33, resulting in 22 eggs. We fertilized those this year and have 9 day-5 blastocysts: 3 normal and 6 abnormal. We’d really like to have 3 kids and are planning to use the 3 normal first. We are debating doing another round of IVF before trying for our first FET so I am younger at the time of another egg retrieval if all 3 normal embryos don’t work. We are wondering if you would recommend transferring any of our abnormal embryos and if you would recommend doing it first so we know better whether we should consider another round of IVF or last in case the others work. Here are the PGS test results for our abnormal embryos:
#1. 45,XX,-21
#2. 46,XX,del(1)(q43) (mos)
#3. 47,XY,+10 (mos)
#4. 45,X (mos)
#5. 45,XX,-16
#6 47,XX,+22
Are there any of those you would recommend transferring? Thank you in advance for your thoughts.
#s 1,3,5 & 6 could ber mosaic.
Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or pre-implantation embryo development, and represents a major cause of early pregnancy loss. About a decade ago, I and an associate, Levent Keskintepe Ph.D were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3 fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.
Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly , summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.
Thus by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.
The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.” As stated, some mosaic embryos will In the process of subsequent cell replication convert to the normal euploid state (i.e. autocorrect)
It is against this background, that an ever increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1.Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2.“Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically euploid early embryo mutate and become aneuploid. This is referred to as mosaicism. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will be “competent” and capable of propagating a normal conceptus.
Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to differentiate between these two varieties of aneuploidy would be of considerable clinical value. And would provide a strong argument in favor of preserving certain aneuploid embryos for future dispensation.
Aneuploidy, involves the addition (trisomy) or subtraction (monosomy) of one chromosome in a given pair. As previously stated, some aneuploidies are meiotic in origin while others are mitotic “mosaics”. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve more than a single pair (i.e. complex aneuploidy). Aside from monosomy involving absence of the y-sex chromosome (i.e. XO) which can resulting in a live birth (Turner syndrome) all monosomies involving autosomes (non-sex chromosomes) are lethal and will not result in viable offspring). Some autosomal meiotic aneuploidies, especially trisomies 13, 18, 21, can progress to viable, but severely chromosomally defective babies. All other meiotic autosomal trisomies will almost invariably, either not attach to the uterine lining or upon attachment, will soon be rejected. All forms of meiotic aneuploidy are irreversible while mitotic aneuploidy (“mosaicism) often autocorrects in the uterus. Most complex aneuploidies are meiotic in origin and will almost invariably fail to propagate viable pregnancies.
There is presently no microscopic or genetic test that can reliable differentiate between meiotic and mitotic aneuploidy. Notwithstanding this, the fact that some “mosaic” embryos can autocorrect in the uterus, makes a strong argument in favor of transferring aneuploid of embryos in the hope that the one(s) transferred might be “mosaic” and might propagate viable healthy pregnancies. On the other hand, it is the fear that embryo aneuploidy might result in a chromosomally abnormal baby that has led many IVF physicians to strongly oppose the transfer of any aneuploid embryos to the uterus.
While certain meiotic aneuploid trisomies (e.g. trisomies 13, 18, & 21) can and sometimes do result in chromosomally defective babies, no other meiotic autosomal trisomies can do so. Thus the transfer of trisomic embryos in the hope that one or more might be mosaic, should exclude the use of embryos with trisomies 13, 18 or 21. Conversely, no autosomal monosomic embryos are believed to be capable of resulting in viable pregnancies, thereby making the transfer of autosomally monosomic embryos, in the hope that they are “mosaic”, a far less risky proposition. Needless to say, if such action is being contemplated, it is absolutely essential to make full disclosure to the patient (s) , and to insure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.
Good luck!
Geoff Sher